Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells

Clinical trials evaluating cardiac progenitor cells (CPC) demonstrated feasibility and safety, but no clear functional benefits. Therefore a deeper understanding of CPC biology is warranted to inform strategies capable to enhance their therapeutic potential. Here we have defined, using a label-free proteomic approach, the differential cytoplasmic and nuclear compartments of human CPC (hCPC). Global analysis of cytoplasmic repertoire in hCPC suggested an important hypoxia response capacity and active collagen metabolism. In addition, comparative analysis of the nuclear protein compartment identified a significant regulation of a small number of proteins in hCPC versus human mesenchymal stem cells (hMSC). Two proteins significantly upregulated in the hCPC nuclear compartment, IL1A and IMP3, showed also a parallel increase in mRNA expression in hCPC versus hMSC, and were studied further. IL1A, subjected to an important post-transcriptional regulation, was demonstrated to act as a dual-function cytokine with a plausible role in apoptosis regulation. The knockdown of the mRNA binding protein (IMP3) did not negatively impact hCPC viability, but reduced their proliferation and migration capacity. Analysis of a panel of putative candidate genes identified HMGA2 and PTPRF as IMP3 targets in hCPC. Therefore, they are potentially involved in hCPC proliferation/migration regulation.

Automated summary

This study investigated the protein composition of cardiac progenitor cells (CPC) and found that they exhibit hypoxia response capacity and active collagen metabolism. The study also identified specific proteins that are significantly regulated in the nuclear compartment of CPC compared to human mesenchymal stem cells (hMSC). Two proteins, IL1A and IMP3, were found to be upregulated in both nuclear and mRNA expression, and further investigation revealed their potential roles in apoptosis regulation and proliferation/migration regulation, respectively.